The focus of our research program is to understand the role of coaggregation in bacterial accretion of early colonizing bacteria on a clean tooth surface. The primary colonizers include actinomyces and streptococci. Antiserum against the 34.8-kDa surface-adhesin, ScaA, from Streptococcus gordonii PK488 cross reacts with a similar size protein from all 14 streptococcal strains so far tested that coaggregate with Actinomyces naeslundii PK606. The sequence of the 6.125 kb clone that contains scaA revealed six open reading frames. The adhesin gene is located adjacent to two genes encoding an ATP-binding protein and a hydrophobic membrane protein. These three genes are homologous to a cassette of genes encoding binding-protein dependent transport systems in several other bacteria. ScaA is a lipoprotein which probably is anchored in the cell membrane while its adhesin binding site is exposed to the environment. Two other oral streptococci also have the same genetic organization of these genes, suggesting that the adhesin is a critical function for colonization of oral streptococci. A 100-kDa protein thought to mediate intrageneric coaggregation among streptococci is absent in several spontaneous mutants and one transposon-inactivated mutant of Streptococcus gordonii DL1. Two potential coaggregation-mediating adhesins from Actinomyces serovar WVA963 strain PK1259 have been identified. Binding of oral actinomyces to defined glycolipid molecules appears to follow the sema specificity exhibited by the actinomyces coaggregations with oral streptococci. The long range goal of these studies, collectively, is to elucidate the molecular mechanisms responsible for bacterial colonization in the human oral ecosystem.